Table 1

Diseases associated with TDP-43 pathology

DiseasePredominant pathologyCo-occurrence of
TDP-43 pathology
Associated genes
Classic ALSTDP-43n.a.ALS2, SETX, TARDBP, VAPB, ANG, UBQLN2, OPTN, PFN1, UNC13a, NEK1, C21orf2, SIGMAR1, DCTN1, MATR3, VCP, hnRNPA1/A2b1, NIPA1, TBK1, ATXN2, UBQLN2, SQSTM1
Familial ALS-SOD1SOD1RarelySOD1
Familial ALS-FUSFUSNoFUS
ALS-FTLD, ALS-ci/biTDP-43n.a.TARDBP, CHMP2b, TBK1, UBQLN2, SQSTM1, DCTN1, UNC13a
Classic ALS, ALS-FTLD, FTLDTDP-43n.a.C9orf72
MSP*TDP-43n.a.VCP, hnRNPA1, hnRNPA2b1, SQSTM1
FTLDTDP-43n.a.CHMP2b, GRN, SQSTM1, OPTN, TBK1, ATXN2
FTLDFUSNo
FTLDTauNoMAPT
Alzheimer’s diseaseβ-Amyloid, tauYesAPOE, APP, PSEN1, PSEN2
Dementia with Lewy bodiesα-SynucleinYesSNCA, APP, PSEN1/PSEN2, MAPT, GBA, APOE
Parkinson diseaseα-SynucleinYesTARDBP, SNCA, Parkin, PINK1, DJ-1, LRRK2, ATP13A2, PLA2G6
Huntington diseaseHuntingtin proteinyesHuntingtin
LATE/CARTSTDP-43, HSn.a.GRN, TMEM106B, ABCC9, KCNMB2, APOE
CTETauYes
Perry diseaseTDP-43n.a.DCTN1
FOSMNTDP-43n.a.SOD1, SQSTM1, VCP, CHCHD10
sIBMTDP-43n.a.
PSPTauYesMAPT, STX6, EIF2AK3
CBDTauYesMAPT
AGDTauYes
  • *Multiple system proteinopathy-A familial disorder in which patients present with ALS, FTLD, inclusion body myositis, Paget’s disease of the bone or combinations of these phenotypes.

  • ALS, amyotrophic lateral sclerosis; bi, behavioural impairment; CARTS, cerebral age-related TDP-43 with sclerosis; ci, cognitive impairment; CTE, chronic traumatic encephalopathy; FOSMN, facial onset sensory and motor neuronopathy; FTLD, frontotemporal lobar degeneration; HS, hippocampal sclerosis; LATE, limbic-predominant age-related TDP-43 encephalopathy; n.a., not applicable; PPA, primary progressive aphasia; sIBM, sporadic inclusion body myositis; TDP-43, TAR DNA-binding protein 43.